Associations between COVID-19 therapies and outcomes in rural and urban America: A multisite, temporal analysis from the Alpha to Omicron SARS-CoV-2 variants.

PURPOSE: To investigate the enduring disparities in adverse COVID-19 events between urban and rural communities in the United States, focusing on the effects of SARS-CoV-2 vaccination and therapeutic advances on patient outcomes. METHODS: Using National COVID Cohort Collaborative (N3C) data from 2021 to 2023, this retrospective cohort study examined COVID-19 hospitalization, inpatient death, and other adverse events. Populations were categorized into urban, urban-adjacent rural (UAR), and nonurban-adjacent rural (NAR). Adjustments included demographics, variant-dominant waves, comorbidities, region, and SARS-CoV-2 treatment and vaccination. Statistical methods included Kaplan-Meier survival estimates, multivariable logistic, and Cox regression. FINDINGS: The study included 3,018,646 patients, with rural residents constituting 506,204. These rural dwellers were older, had more comorbidities, and were less vaccinated than their urban counterparts. Adjusted analyses revealed higher hospitalization odds in UAR and NAR (aOR 1.07 [1.05-1.08] and 1.06 [1.03-1.08]), greater inpatient death hazard (aHR 1.30 [1.26-1.35] UAR and 1.37 [1.30-1.45] NAR), and greater risk of other adverse events compared to urban dwellers. Delta increased, while Omicron decreased, inpatient adverse events relative to pre-Delta, with rural disparities persisting throughout. Treatment effectiveness and vaccination were similarly protective across all cohorts, but dexamethasone post-ventilation was effective only in urban areas. Nirmatrelvir/ritonavir and molnupiravir better protected rural residents against hospitalization. CONCLUSIONS: Despite advancements in treatment and vaccinations, disparities in adverse COVID-19 outcomes persist between urban and rural communities. The effectiveness of some therapeutic agents appears to vary based on rurality, suggesting a nuanced relationship between treatment and geographic location while highlighting the need for targeted rural health care strategies.

Avenues for Strengthening PCORnet's Capacity to Advance Patient-Centered Economic Outcomes in Patient-Centered Outcomes Research (PCOR).

PCORnet, the National Patient-Centered Clinical Research Network, provides the ability to conduct prospective and observational pragmatic research by leveraging standardized, curated electronic health records data together with patient and stakeholder engagement. PCORnet is funded by the Patient-Centered Outcomes Research Institute (PCORI) and is composed of 8 Clinical Research Networks that incorporate at total of 79 health system "sites." As the network developed, linkage to commercial health plans, federal insurance claims, disease registries, and other data resources demonstrated the value in extending the networks infrastructure to provide a more complete representation of patient's health and lived experiences. Initially, PCORnet studies avoided direct economic comparative effectiveness as a topic. However, PCORI's authorizing law was amended in 2019 to allow studies to incorporate patient-centered economic outcomes in primary research aims. With PCORI's expanded scope and PCORnet's phase 3 beginning in January 2022, there are opportunities to strengthen the network's ability to support economic patient-centered outcomes research. This commentary will discuss approaches that have been incorporated to date by the network and point to opportunities for the network to incorporate economic variables for analysis, informed by patient and stakeholder perspectives. Topics addressed include: (1) data linkage infrastructure; (2) commercial health plan partnerships; (3) Medicare and Medicaid linkage; (4) health system billing-based benchmarking; (5) area-level measures; (6) individual-level measures; (7) pharmacy benefits and retail pharmacy data; and (8) the importance of transparency and engagement while addressing the biases inherent in linking real-world data sources.

Associations between COVID-19 therapies and inpatient gastrointestinal bleeding: A multisite retrospective study.

Little data is available regarding the incidence of gastrointestinal bleeding in adults hospitalized with COVID-19 infection and the influence of patient comorbidities and demographics, COVID-19 therapies, and typical medications used. In this retrospective study, we utilized the National COVID Cohort Collaborative to investigate the primary outcome of the development of gastrointestinal bleeding in 512 467 hospitalized US adults (age >18 years) within 14 days of a COVID-19 infection and the influence of demographics, comorbidities, and selected medications. Gastrointestinal bleeding developed in 0.44% of patients hospitalized with COVID-19. Comorbidities associated with gastrointestinal bleeding include peptic ulcer disease (adjusted odds ratio [aOR] 10.2), obesity (aOR 1.27), chronic kidney disease (aOR 1.20), and tobacco use disorder (aOR 1.28). Lower risk of gastrointestinal bleeding was seen among women (aOR 0.76), Latinx (aOR 0.85), and vaccinated patients (aOR 0.74). Dexamethasone alone or with remdesivir was associated with lower risk of gastrointestinal bleeding (aOR 0.69 and aOR 0.83, respectively). Remdesivir monotherapy was associated with upper gastrointestinal bleeding (aOR 1.25). Proton pump inhibitors were more often prescribed in patients with gastrointestinal bleeding, likely representing treatment for gastrointestinal bleeding rather than a risk factor for its development. In adult patients hospitalized with COVID-19, the use of dexamethasone alone or in combination with remdesivir is negatively associated with gastrointestinal bleeding. Remdesivir monotherapy is associated with increased risk of upper gastrointestinal bleeding.

Disruption in Blood Pressure Control With the COVID-19 Pandemic: The PCORnet Blood Pressure Control Laboratory.

OBJECTIVE: To explore trends in blood pressure (BP) control before and during the COVID-19 pandemic. PATIENTS AND METHODS: Health systems participating in the National Patient-Centered Clinical Research Network (PCORnet) Blood Pressure Control Laboratory Surveillance System responded to data queries, producing 9 BP control metrics. Averages of the BP control metrics (weighted by numbers of observations in each health system) were calculated and compared between two 1-year measurement periods (January 1, 2019, through December 31, 2019, and January 1, 2020, through December 31, 2020). RESULTS: Among 1,770,547 hypertensive persons in 2019, BP control to <140/<90 mm Hg varied across 24 health systems (range, 46%-74%). Reduced BP control occurred in most health systems with onset of the COVID-19 pandemic; the weighted average BP control was 60.5% in 2019 and 53.3% in 2020. Reductions were also evident for BP control to <130/<80 mm Hg (29.9% in 2019 and 25.4% in 2020) and improvement in BP (reduction of 10 mm Hg in systolic BP or achievement of systolic BP <140 mm Hg; 29.7% in 2019 and 23.8% in 2020). Two BP control process metrics exhibited pandemic-associated disruption: repeat visit in 4 weeks after a visit with uncontrolled hypertension (36.7% in 2019 and 31.7% in 2020) and prescription of fixed-dose combination medications among those with 2 or more drug classes (24.6% in 2019 and 21.5% in 2020). CONCLUSION: BP control decreased substantially during the COVID-19 pandemic, with a corresponding reduction in follow-up health care visits among persons with uncontrolled hypertension. It is unclear whether the observed decline in BP control during the pandemic will contribute to future cardiovascular events.

Seasonal variation in blood pressure control across US health systems.

OBJECTIVE: We aimed to characterize seasonal variation in US population-based blood pressure (BP) control and BP-related metrics and evaluate the association between outdoor temperature and BP control variation. METHODS: We queried electronic health records (EHRs) from 26 health systems, representing 21 states, to summarize BP metrics by quarters of 12-month periods from January 2017 to March 2020. Patients with at least one ambulatory visit during the measurement period and a hypertension diagnosis during the first 6 months or prior to the measurement period were included. Changes in BP control, BP improvement, medication intensification, average SBP reduction after medication intensification across quarters and association with outdoor temperature were analyzed using weighted generalized linear models with repeated measures. RESULTS: Among 1 818 041 people with hypertension, the majority were more than 65 years of age (52.2%), female (52.1%), white non-Hispanic (69.8%) and had stage 1/2 hypertension (64.8%). Overall, BP control and process metrics were highest in quarters 2 and 3, and lowest in quarters 1 and 4. Quarter 2 had the highest percentage of improved BP (31.95 ±â€Š0.90%) and average SBP reduction after medication intensification (16 ±â€Š0.23 mmHg). Quarter 3 had the highest percentage of BP controlled (62.25 ±â€Š2.55%) and lowest with medication intensification (9.73 ±â€Š0.60%). Results were largely consistent in adjusted models. Average temperature was associated with BP control metrics in unadjusted models, but associations were attenuated following adjustment. CONCLUSION: In this large, national, EHR-based study, BP control and BP-related process metrics improved during spring/summer months, but outdoor temperature was not associated with performance following adjustment for potential confounders.

Community risks for SARS-CoV-2 infection among fully vaccinated US adults by rurality: A retrospective cohort study from the National COVID Cohort Collaborative.

BACKGROUND: While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) among fully vaccinated persons by rurality. METHODS: We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, Cox Proportional Hazards models assessed the risk of infection among adults without documented vaccinations. We secondarily assessed the odds of hospitalization and adverse COVID-19 events based on vaccination status using multivariable logistic regression during the study period. RESULTS: Our study population included 566,128 vaccinated and 1,724,546 adults without documented vaccination. Among vaccinated persons, rurality was associated with an increased risk of BTI (adjusted hazard ratio [aHR] 1.53, 95% confidence interval [CI] 1.42-1.64, for urban-adjacent rural and 1.65, 1.42-1.91, for nonurban-adjacent rural) compared to urban dwellers. Compared to low vaccine-hesitant counties, higher risks of BTI were associated with medium (1.07, 1.02-1.12) and high (1.33, 1.23-1.43) vaccine-hesitant counties. Compared to counties with high vaccination rates, a higher risk of BTI was associated with dwelling in counties with low vaccination rates (1.34, 1.27-1.43) but not medium vaccination rates (1.00, 0.95-1.07). Community factors were also associated with higher odds of SARS-CoV-2 infection among persons without a documented vaccination. Vaccinated persons with SARS-CoV-2 infection during the study period had significantly lower odds of hospitalization and adverse events across all geographic areas and community exposures. CONCLUSIONS: Our findings suggest that community factors are associated with an increased risk of BTI, particularly in rural areas and counties with high vaccine hesitancy. Communities, such as those in rural and disproportionately vaccine hesitant areas, and certain groups at high risk for adverse breakthrough events, including immunosuppressed/compromised persons, should continue to receive public health focus, targeted interventions, and consistent guidance to help manage community spread as vaccination protection wanes.

Preoperative Depression Status and 5 Year Metabolic and Bariatric Surgery Outcomes in the PCORnet Bariatric Study Cohort.

OBJECTIVE: To examine whether depression status before metabolic and bariatric surgery (MBS) influenced 5-year weight loss, diabetes, and safety/utilization outcomes in the PCORnet Bariatric Study. SUMMARY OF BACKGROUND DATA: Research on the impact of depression on MBS outcomes is inconsistent with few large, long-term studies. METHODS: Data were extracted from 23 health systems on 36,871 patients who underwent sleeve gastrectomy (SG; n=16,158) or gastric bypass (RYGB; n=20,713) from 2005-2015. Patients with and without a depression diagnosis in the year before MBS were evaluated for % total weight loss (%TWL), diabetes outcomes, and postsurgical safety/utilization (reoperations, revisions, endoscopy, hospitalizations, mortality) at 1, 3, and 5 years after MBS. RESULTS: 27.1% of SG and 33.0% of RYGB patients had preoperative depression, and they had more medical and psychiatric comorbidities than those without depression. At 5 years of follow-up, those with depression, versus those without depression, had slightly less %TWL after RYGB, but not after SG (between group difference = 0.42%TWL, P = 0.04). However, patients with depression had slightly larger HbA1c improvements after RYGB but not after SG (between group difference = - 0.19, P = 0.04). Baseline depression did not moderate diabetes remission or relapse, reoperations, revision, or mortality across operations; however, baseline depression did moderate the risk of endoscopy and repeat hospitalization across RYGB versus SG. CONCLUSIONS: Patients with depression undergoing RYGB and SG had similar weight loss, diabetes, and safety/utilization outcomes to those without depression. The effects of depression were clinically small compared to the choice of operation.

Higher hospitalization and mortality rates among SARS-CoV-2-infected persons in rural America.

PURPOSE: Rural communities are among the most underserved and resource-scarce populations in the United States. However, there are limited data on COVID-19 outcomes in rural America. This study aims to compare hospitalization rates and inpatient mortality among SARS-CoV-2-infected persons stratified by residential rurality. METHODS: This retrospective cohort study from the National COVID Cohort Collaborative (N3C) assesses 1,033,229 patients from 44 US hospital systems diagnosed with SARS-CoV-2 infection between January 2020 and June 2021. Primary outcomes were hospitalization and all-cause inpatient mortality. Secondary outcomes were utilization of supplemental oxygen, invasive mechanical ventilation, vasopressor support, extracorporeal membrane oxygenation, and incidence of major adverse cardiovascular events or hospital readmission. The analytic approach estimates 90-day survival in hospitalized patients and associations between rurality, hospitalization, and inpatient adverse events while controlling for major risk factors using Kaplan-Meier survival estimates and mixed-effects logistic regression. FINDINGS: Of 1,033,229 diagnosed COVID-19 patients included, 186,882 required hospitalization. After adjusting for demographic differences and comorbidities, urban-adjacent and nonurban-adjacent rural dwellers with COVID-19 were more likely to be hospitalized (adjusted odds ratio [aOR] 1.18, 95% confidence interval [CI], 1.16-1.21 and aOR 1.29, CI 1.24-1.1.34) and to die or be transferred to hospice (aOR 1.36, CI 1.29-1.43 and 1.37, CI 1.26-1.50), respectively. All secondary outcomes were more likely among rural patients. CONCLUSIONS: Hospitalization, inpatient mortality, and other adverse outcomes are higher among rural persons with COVID-19, even after adjusting for demographic differences and comorbidities. Further research is needed to understand the factors that drive health disparities in rural populations.

Mapping Clinical Documents to the Logical Observation Identifiers, Names and Codes (LOINC) Document Ontology using Electronic Health Record Systems Structured Metadata.

As Electronic Health Record (EHR) systems increase in usage, organizations struggle to maintain and categorize clinical documentation so it can be used for clinical care and research. While prior research has often employed natural language processing techniques to categorize free text documents, there are shortcomings relative to computational scalability and the lack of key metadata within notes' text. This study presents a framework that can allow institutions to map their notes to the LOINC document ontology using a Bag of Words approach. After preliminary manual value- set mapping, an automated pipeline that leverages key dimensions of metadata from structured EHR fields aligns the notes with the dimensions of the document ontology. This framework resulted in 73.4% coverage of EHR documents, while also mapping 132 million notes in less than 2 hours; an order of magnitude more efficient than NLP based methods.

Impact of malnutrition on clinical outcomes in patients diagnosed with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is now the third leading cause of death in the United States. Malnutrition in hospitalized patients increases risk of complications. However, the effect of malnutrition on outcomes in patients infected is unclear. This study aims to identify the impact of malnutrition on mortality and adverse hospital events in patients hospitalized with COVID-19. METHODS: This study used data from the National COVID Cohort Collaborative (N3C), a COVID-19 repository containing harmonized, longitudinal electronic health record data from US health systems. Malnutrition was categorized into three groups based on condition diagnosis: (1) none documented, (2) history of malnutrition, and (3) hospital-acquired malnutrition. Multivariable logistic regression was performed to determine whether malnutrition was associated with mortality and adverse events, including mechanical ventilation, acute respiratory distress syndrome, extracorporeal membrane oxygenation, and hospital-acquired pressure injury, in hospitalized patients with COVID-19. RESULTS: Of 343,188 patients hospitalized with COVID-19, 11,206 had a history of malnutrition and 15,711 had hospital-acquired malnutrition. After adjustment for potential confounders, odds of mortality were significantly higher in patients with a history of malnutrition (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.63-1.79; P < 0.001) and hospital-acquired malnutrition (OR, 2.5; 95% CI, 2.4-2.6; P < 0.001). Adjusted odds of adverse hospital events were also significantly elevated in both malnutrition groups. CONCLUSIONS: Results indicate the risk of mortality and adverse inpatient events in adults with COVID-19 is significantly higher in patients with malnutrition. Prevention, diagnosis, and treatment of malnutrition could be a key component in improving outcomes in these patients.

COVID-19 patients with documented alcohol use disorder or alcohol-related complications are more likely to be hospitalized and have higher all-cause mortality.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) has affected every country globally, with hundreds of millions of people infected with the SARS-CoV-2 virus and over 6 million deaths to date. It is unknown how alcohol use disorder (AUD) affects the severity and mortality of COVID-19. AUD is known to increase the severity and mortality of bacterial pneumonia and the risk of developing acute respiratory distress syndrome. Our objective is to determine whether individuals with AUD have increased severity and mortality from COVID-19. METHODS: We utilized a retrospective cohort study of inpatients and outpatients from 44 centers participating in the National COVID Cohort Collaborative. All were adult COVID-19 patients with and without documented AUDs. RESULTS: We identified 25,583 COVID-19 patients with an AUD and 1,309,445 without. In unadjusted comparisons, those with AUD had higher odds of hospitalization (odds ratio [OR] 2.00, 95% confidence interval [CI] 1.94 to 2.06, p < 0.001). After adjustment for age, sex, race/ethnicity, smoking, body mass index, and comorbidities, individuals with an AUD still had higher odds of requiring hospitalization (adjusted OR [aOR] 1.51, CI 1.46 to 1.56, p < 0.001). In unadjusted comparisons, individuals with AUD had higher odds of all-cause mortality (OR 2.18, CI 2.05 to 2.31, p < 0.001). After adjustment as above, individuals with an AUD still had higher odds of all-cause mortality (aOR 1.55, CI 1.46 to 1.65, p < 0.001). CONCLUSION: This work suggests that AUD can increase the severity and mortality of COVID-19 infection. This reinforces the need for clinicians to obtain an accurate alcohol history from patients hospitalized with COVID-19. For this study, our results are limited by an inability to quantify the daily drinking habits of the participants. Studies are needed to determine the mechanisms by which AUD increases the severity and mortality of COVID-19.

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and COVID-19-related outcomes: A patient-level analysis of the PCORnet blood pressure control lab.

SARS-CoV-2 accesses host cells via angiotensin-converting enzyme-2, which is also affected by commonly used angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), raising concerns that ACEI or ARB exposure may portend differential COVID-19 outcomes. In parallel cohort studies of outpatient and inpatient COVID-19-diagnosed adults with hypertension, we assessed associations between antihypertensive exposure (ACEI/ARB vs. non-ACEI/ARB antihypertensives, as well as between ACEI- vs. ARB) at the time of COVID-19 diagnosis, using electronic health record data from PCORnet health systems. The primary outcomes were all-cause hospitalization or death (outpatient cohort) or all-cause death (inpatient), analyzed via Cox regression weighted by inverse probability of treatment weights. From February 2020 through December 9, 2020, 11,246 patients (3477 person-years) and 2200 patients (777 person-years) were included from 17 health systems in outpatient and inpatient cohorts, respectively. There were 1015 all-cause hospitalization or deaths in the outpatient cohort (incidence, 29.2 events per 100 person-years), with no significant difference by ACEI/ARB use (adjusted HR 1.01; 95% CI 0.88, 1.15). In the inpatient cohort, there were 218 all-cause deaths (incidence, 28.1 per 100 person-years) and ACEI/ARB exposure was associated with reduced death (adjusted HR, 0.76; 95% CI, 0.57, 0.99). ACEI, versus ARB exposure, was associated with higher risk of hospitalization in the outpatient cohort, but no difference in all-cause death in either cohort. There was no evidence of effect modification across pre-specified baseline characteristics. Our results suggest ACEI and ARB exposure have no detrimental effect on hospitalizations and may reduce death among hypertensive patients diagnosed with COVID-19.

Categorizing metadata to help mobilize computable biomedical knowledge.

INTRODUCTION: Computable biomedical knowledge artifacts (CBKs) are digital objects conveying biomedical knowledge in machine-interpretable structures. As more CBKs are produced and their complexity increases, the value obtained from sharing CBKs grows. Mobilizing CBKs and sharing them widely can only be achieved if the CBKs are findable, accessible, interoperable, reusable, and trustable (FAIR+T). To help mobilize CBKs, we describe our efforts to outline metadata categories to make CBKs FAIR+T. METHODS: We examined the literature regarding metadata with the potential to make digital artifacts FAIR+T. We also examined metadata available online today for actual CBKs of 12 different types. With iterative refinement, we came to a consensus on key categories of metadata that, when taken together, can make CBKs FAIR+T. We use subject-predicate-object triples to more clearly differentiate metadata categories. RESULTS: We defined 13 categories of CBK metadata most relevant to making CBKs FAIR+T. Eleven of these categories (type, domain, purpose, identification, location, CBK-to-CBK relationships, technical, authorization and rights management, provenance, evidential basis, and evidence from use metadata) are evident today where CBKs are stored online. Two additional categories (preservation and integrity metadata) were not evident in our examples. We provide a research agenda to guide further study and development of these and other metadata categories. CONCLUSION: A wide variety of metadata elements in various categories is needed to make CBKs FAIR+T. More work is needed to develop a common framework for CBK metadata that can make CBKs FAIR+T for all stakeholders.

Tracking Blood Pressure Control Performance and Process Metrics in 25 US Health Systems: The PCORnet Blood Pressure Control Laboratory.

Background The National Patient-Centered Clinical Research Network Blood Pressure Control Laboratory Surveillance System was established to identify opportunities for blood pressure (BP) control improvement and to provide a mechanism for tracking improvement longitudinally. Methods and Results We conducted a serial cross-sectional study with queries against standardized electronic health record data in the National Patient-Centered Clinical Research Network (PCORnet) common data model returned by 25 participating US health systems. Queries produced BP control metrics for adults with well-documented hypertension and a recent encounter at the health system for a series of 1-year measurement periods for each quarter of available data from January 2017 to March 2020. Aggregate weighted results are presented overall and by race and ethnicity. The most recent measurement period includes data from 1 737 995 patients, and 11 956 509 patient-years were included in the trend analysis. Overall, 15% were Black, 52% women, and 28% had diabetes. BP control (<140/90 mm Hg) was observed in 62% (range, 44%-74%) but varied by race and ethnicity, with the lowest BP control among Black patients at 57% (odds ratio, 0.79; 95% CI, 0.66-0.94). A new class of antihypertensive medication (medication intensification) was prescribed in just 12% (range, 0.6%-25%) of patient visits where BP was uncontrolled. However, when medication intensification occurred, there was a large decrease in systolic BP (≈15 mm Hg; range, 5-18 mm Hg). Conclusions Major opportunities exist for improving BP control and reducing disparities, especially through consistent medication intensification when BP is uncontrolled. These data demonstrate substantial room for improvement and opportunities to close health equity gaps.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

BACKGROUND: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).

Use of Comprehensive Participatory Planning and Evaluation in Rural Patient Engagement.

Comprehensive participatory planning and evaluation (CPPE), a model used in community engagement research, has not been applied to patient engagement in research. We describe our methodology and interim results using CPPE in a project focused on improving research engagement of rural and distant patients and stakeholders. Specifically, we describe our development of a causal map and the subsequent use of the map to guide patient and stakeholder-driven evaluation.

Impact of the Early Phase of the COVID-19 Pandemic on US Healthcare Workers: Results from the HERO Registry.

BACKGROUND: The HERO registry was established to support research on the impact of the COVID-19 pandemic on US healthcare workers. OBJECTIVE: Describe the COVID-19 pandemic experiences of and effects on individuals participating in the HERO registry. DESIGN: Cross-sectional, self-administered registry enrollment survey conducted from April 10 to July 31, 2020. SETTING: Participants worked in hospitals (74.4%), outpatient clinics (7.4%), and other settings (18.2%) located throughout the nation. PARTICIPANTS: A total of 14,600 healthcare workers. MAIN MEASURES: COVID-19 exposure, viral and antibody testing, diagnosis of COVID-19, job burnout, and physical and emotional distress. KEY RESULTS: Mean age was 42.0 years, 76.4% were female, 78.9% were White, 33.2% were nurses, 18.4% were physicians, and 30.3% worked in settings at high risk for COVID-19 exposure (e.g., ICUs, EDs, COVID-19 units). Overall, 43.7% reported a COVID-19 exposure and 91.3% were exposed at work. Just 3.8% in both high- and low-risk settings experienced COVID-19 illness. In regression analyses controlling for demographics, professional role, and work setting, the risk of COVID-19 illness was higher for Black/African-Americans (aOR 2.32, 99% CI 1.45, 3.70, p < 0.01) and Hispanic/Latinos (aOR 2.19, 99% CI 1.55, 3.08, p < 0.01) compared with Whites. Overall, 41% responded that they were experiencing job burnout. Responding about the day before they completed the survey, 53% of participants reported feeling tired a lot of the day, 51% stress, 41% trouble sleeping, 38% worry, 21% sadness, 19% physical pain, and 15% anger. On average, healthcare workers reported experiencing 2.4 of these 7 distress feelings a lot of the day. CONCLUSIONS: Healthcare workers are at high risk for COVID-19 exposure, but rates of COVID-19 illness were low. The greater risk of COVID-19 infection among race/ethnicity minorities reported in the general population is also seen in healthcare workers. The HERO registry will continue to monitor changes in healthcare worker well-being during the pandemic. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04342806.

Rationale and Design of the Aspirin Dosing-A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) Trial.

Importance: Determining the right dosage of aspirin for the secondary prevention treatment of atherosclerotic cardiovascular disease (ASCVD) remains an unanswered and critical question. Objective: To report the rationale and design for a randomized clinical trial to determine the optimal dosage of aspirin to be used for secondary prevention of ASCVD, using an innovative research method. Design, Setting, and Participants: This pragmatic, open-label, patient-centered, randomized clinical trial is being conducted in 15 000 patients within the National Patient-Centered Clinical Research Network (PCORnet), a distributed research network of partners including clinical research networks, health plan research networks, and patient-powered research networks across the United States. Patients with established ASCVD treated in routine clinical practice within the network are eligible. Patient recruitment began in April 2016. Enrollment was completed in June 2019. Final follow-up is expected to be completed by June 2020. Interventions: Participants are randomized on a web platform in a 1:1 fashion to either 81 mg or 325 mg of aspirin daily. Main Outcomes and Measures: The primary efficacy end point is the composite of all-cause mortality, hospitalization for nonfatal myocardial infarction, or hospitalization for a nonfatal stroke. The primary safety end point is hospitalization for major bleeding associated with a blood-product transfusion. End points are captured through regular queries of the health systems' common data model within the structure of PCORnet's distributed data environment. Conclusions and Relevance: As a pragmatic study and the first interventional trial conducted within the PCORnet electronic data infrastructure, this trial is testing several unique and innovative operational approaches that have the potential to disrupt and transform the conduct of future patient-centered randomized clinical trials by evaluating treatments integrated in clinical practice while at the same time determining the optimal dosage of aspirin for secondary prevention of ASCVD. Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.